ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.703G>C (p.Glu235Gln)

dbSNP: rs1353807357
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001248894 SCV001422575 uncertain significance Maturity-onset diabetes of the young type 3 2020-01-22 criteria provided, single submitter curation The p.Glu235Gln variant in HNF1A has been reported in an Indian individual with maturity-onset diabetes of the young (PMID: 19336507), and has been identified in 0.003% (1/30604) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs1353807357). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. In vitro functional studies provide some evidence that the p.Glu235Gln variant may slightly impact protein function (PMID: 26853433). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. The p.Glu235Gln variant is located in a region of HNF1A that is essential to protein folding and stability, suggesting that this variant is in a functional domain and slightly supports pathogenicity (PMID: 26853433). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PS3_Supporting, PM1_Supporting (Richards 2015).
Molecular Genetics, Madras Diabetes Research Foundation RCV002051925 SCV002318408 likely benign Maturity onset diabetes mellitus in young criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002051925 SCV002604995 uncertain risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs1353807357 with MODY3.

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